Secondary Structures in Proteins
Secondary Structures in Protein entail the local folded structures forming within a polypeptide following interactions between backbone atoms. They entail the polypeptide chain, which is not part of the R groups. The most common structures are the β pleated and α helix sheets (Taechalertpaisarn, 2019). Hydrogen bonds hold the structure in shape that forms between the amino H and carbonyl O of different amino acids. This paper explains proteins’ common secondary structures and signaling lipids from Arachidonic Acid.
The carbon and nitrogen atoms have a high magnitude bond angle of approximately 110° making it impossible to form a straight line in a peptide chain. Every carbon and nitrogen atom tends to rotate limiting its flexibility. Peptide chains develop an asymmetric helical shape because almost all amino acids are asymmetric l-amino acids (Taechalertpaisarn, 2019). Glycine is the only exceptional amino acid that does not have the shape. Notably, certain fibrous proteins have elongated helices appearing on a straight screw-like axis. All peptides usually have common chains determining their structural features. The secondary structure is developed following the peptides effect and bonding.
Beta sheets are developed following the H-bonding occurring in adjacent chains between backbone residues. The sheet forms following the creation of a single chain when H bonds the neighboring chains where the acceptor (carbonyl) and donor (amide) atoms point sideways instead of forming a straight chain. They can be either parallel or antiparallel determining the developed shape. The parallel beta sheets occur when the chain points in a similar direction in the amino-carboxyl terminus while the antiparallel shape is noted when adjacent chains take a matching point.
At least two polypeptide segments form a chain next to each other resulting in the development of a sheet-like structure in a β-pleated sheet. Hydrogen bonds hold the chain together where they form between amino and carboxyl groups in the backbone and extend below and above the plane. The sheet may point in the same direction or take a parallel position implying that their C- and N- termini tend to match up (Taechalertpaisarn, 2019). They can also take an antiparallel position where it points in opposite directions suggesting that one strand’s N-terminus are placed next to another C-terminus.
Hydrogen bonds join amino H (N-H) and the carbonyl (C=O) of a different amino in the α helix sheet. Amino H (N-H) is usually four down the chain in amino acid. The bonding pattern influences the polypeptide chain to form a helical structure looking like a curved ribbon where each contains 3-6 amino acids. This implies that the R groups can interact freely because they stick outward in a helix structure.
Some amino acids are less or more likely to be found in either a β pleated or α-helices sheet. The term “helix breaker” is sometimes applied to refer to the amino acid proline due to its unusual R group forming a ring after bonding with the amino group. It is usually incompatible with the formation of the helix since it creates a bend noted in the chain. Some of the amino acids found in β-pleated sheets include tyrosine, tryptophan, as well as phenylalanine since their R groups have large ring structures. This is following the many spaces created for the side chains in the β pleated sheet structure (Taechalertpaisarn, 2019). Notably, most of the proteins have both the β pleated sheets and α helices. However, some proteins contain one of these types while others lack either form. The secondary structure can be applied to predict the possibilities of having a tertiary structure since analyzing the amino acid sequence may fail to offer accurate results. The pattern of hydrogen bonding determines the secondary structure of the protein.
Molten globule (MG) is a protein state that is usually less or more compact. They have partially folded confrontations and compact proteins with native substantial and compact secondary structures. Their surface area is highly solvent-exposed hydrophobic and it has a limited detectable tertiary structure due to its native state. They have a solid state similar to tertiary structures since they lack specific amino acid residues that are tight packing (Parray et al., 2020). It entails diverse partially folded protein states that can be found in conditions that are slightly denaturing including high temperature, mild denaturant, and low pH.
Cytochrome c is one of the examples of acid-denatured proteins, and it tends to unfold completely in the presence of HCL at pH 2 when salt is unavailable. The MG is a protein folding intermediates marked with native-like compact and perturbed tertiary interaction. It influences the advent of protein aggregation since it is marked by about a 10-30% increase in the gyration radius, intact secondary structure, and loss of tertiary structure (Pedrote et al., 2018). There exists a relationship between the development of MG and N-homocysteinylation.
Signaling Lipids from Arachidonic Acid
The hydrolysis of phospholipids in the presence of phospholipase A2 results in the freeing up of arachidonic acid. The cytosolic phospholipase A2 help generate the arachidonic acid for the signaling purpose. Cyclooxygenase-1 and -2 enzymes facilitate the conversion of the acid into thromboxanes, prostacyclin, and prostaglandins (Dean & Lodhi, 2018). Epoxygenase enzyme triggers the conversion of the acid into epoxyeicosatrienoic acids and hydroxyeicosatetraenoic acids (HETEs) while the 5-lipoxygenase influences the oxidation of arachidonic acid into 5-hydroperoxy-eicosatetraenoic acid.
Some the examples of bioactive lipids are ceramides, steroid hormones, eicosanoids, and diacylglycerols (DAGs). Ceramides are sphingolipids serving many roles including linking internal cell metabolism to external signals, influencing cell differentiation, and apoptosis. It affects cell growth and triggers migration, senescence, and adhesion. Diacylglycerols (DAGs) promote metabolic pathways where they influence membrane function and structure. They activate regulatory proteins by enabling and altering cell-signaling cascades (Dean & Lodhi, 2018). Eicosanoids entail lipid-soluble molecules obtained through the oxidation of arachidonic acid. They take part in vasoconstriction and vasodilation and improvement of the quality of sleep. Steroid hormones entail chemical messengers facilitating the movement of signals from one cell to the next. There are five classes and they have a similar structure and are synthesized from the same cholesterol and parent sterol. They are progestogens (progesterone), androgens, mineralocorticoids, glucocorticoids, and estrogens.
Paracrine signaling is a cellular communication where cells generate signals to influence changes in the neighboring cells affecting their behaviors. Molecules usually diffuse over a limited distance since it influences local actions. Involved cells tend to secrete paracrine into the extracellular environment where it travels to other cells and influences the outcome (Gonzalez-Gonzalez et al., 2017). Lipids usually act as paracrine signaling molecules by binding cell surface receptors of the target cells. Eicosanoids including leukotrienes, prostacyclin, thromboxanes, and prostaglandins are the most important molecules in this function. They act locally in paracrine signaling pathways because they are broken down rapidly.
Bioactive lipids play a role in the signaling in an organism’s cells. They are signaling molecules present in the immune system where that facilitate the proper functioning of the adaptive and innate immune systems. They help maintain structure and order in cells and transfer proteins to the right organelles. Moreover, metabolic pathways usually depend on lipid signals to serve basic cell functions such as exocytosis and endocytosis (Luo, 2018). They also serve the specialized functions of neurons and endocrine cells.
The majority of lipids that serve as the second messenger during cell signaling come from the arachidonic acid (AA) pathway. Lipids play an important role and usually include phospholipids, mono and diglycerides, and sterols. They are structural cell membrane components and energy contributors to metabolism (Luo, 2018). Lipids are also signaling molecules and intracellular transport participants that facilitate the movement of organelles. Apart from the role of storing energy and a passive component, they support signal transduction. The interior components tend to respond to the external part of the cell and environment. The primary messenger refers to the chemical signal influencing the cell response.
The information transmitter does not enter the cell but tends to bind with the surface receptors located on the membrane surface. The communication happens through sensing of a ligand to the outside. This results in the activation of the lipid bilayer at the intracellular or membrane surface (Luo, 2018). Enzymes usually cleave lipid molecules where it functions as the secondary messenger by sending intracellular signals. It binds the intracellular enzyme to trigger processes inside the cell. Lipid signaling facilitates appropriate cell response based on the environmental situation that is likely to affect certain activities.
Lipid signaling entails biological events where the messenger binds a targeted protein such as phosphatase, kinase, or receptor. It entails the propagation of signal or lipid-dependent activation within a cell. Lipids are considered key components of biological membranes sensing extracellular conditions. Signaling involving mediated lipid arises as an attempt to respond to diverse environmental stresses including drought, pathogen attack, and changes in salinity and temperature (Luo, 2018). Many substances serve as signal lipids including fatty acids, sphingolipid, diacylglycerol, and N–acylethanolamine, lysophospholipid, oxylipins, and inositol phosphate. Every lipid class has specific signaling cascades, biosynthetic mechanisms, and biological relevance.
Arachidonic acid (AA) is a polyunsaturated fatty acid and a precursor for many signaling lipids that are present in cell membranes’ phospholipids. Receptor activation influences their release where phospholipase A2 is turned on. The outcome is hydrolyzed sn-2 ester bond and subsequent generation of AA. This initiates various events and the production of many lipid mediators increasing vascular permeability, triggering inflammation, and boosting platelet activation (Luo, 2018). Enzymatic or non-enzymatic pathways can lead to the generation of these mediators. The enzymatic breakdown takes place through lipoxygenase, cytochrome P450s, or the cyclooxygenase pathways resulting in the generation of inflammatory mediators
The nonenzymatic pathway results in the production of free radicals following excess oxidative stress that influences the generation of isoprostanes. In enzymatic breakdown, LOX and P450s pathway tends to metabolize AA to generate hydroxy eicosatetraenoic acids (HETEs). Enzymatic reactions are responsible for most of the pro-inflammatory lipids from the AA metabolism (Luo, 2018). These inflammations serve an essential role in chemotaxis especially neutrophils implying that their presence is an indication of a reaction.
References
Dean, J. M., & Lodhi, I. J. (2018). Structural and functional roles of ether lipids. Protein & Cell, 9(2), 196-206. Web.
Gonzalez-Gonzalez, F. J., Chandel, N. S., Jain, M., & Budinger, G. S. (2017). Reactive oxygen species as signaling molecules in the development of lung fibrosis. Translational Research, 190, 61-68. Web.
Luo, X., Zhao, X., Cheng, C., Li, N., Liu, Y., & Cao, Y. (2018). The implications of signaling lipids in cancer metastasis. Experimental & Molecular Medicine, 50(9), 1-10. Web.
Parray, Z. A., Ahmad, F., Alajmi, M. F., Hussain, A., Hassan, M. I., & Islam, A. (2020). Formation of molten globule state in horse heart cytochrome c under physiological conditions: Importance of soft interactions and spectroscopic approach in crowded milieu. International Journal of Biological Macromolecules, 148, 192-200. Web.
Pedrote, M. M., de Oliveira, G. A., Felix, A. L., Mota, M. F., Marques, M. D. A., Soares, I. N.,… & Silva, J. L. (2018). Aggregation-primed molten globule conformers of the p53 core domain provide potential tools for studying p53C aggregation in cancer. Journal of Biological Chemistry, 293(29), 11374-11387. Web.
Taechalertpaisarn, J., Lyu, R. L., Arancillo, M., Lin, C. M., Perez, L. M., Ioerger, T. R., & Burgess, K. (2019). Correlations between secondary structure and protein-protein interface-mimicry: the interface mimicry hypothesis. Organic & Biomolecular Chemistry, 17(12), 3267-3274. Web.